Deploying Embolic Coils

ABSTRACT

An embolic coil delivery system includes a catheter and an embolic coil disposed within the catheter, the embolic coil including a coil wire and a fiber bundle. A method of producing an embolic coil delivery system includes: advancing a delivery sheath over a distal end of an embolic coil while applying tension to the embolic coil via a retaining device that is attached to the distal end of the embolic coil.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/703,993, filed Dec. 5, 2019, which is a continuation of U.S.application Ser. No. 12/029,990, filed Dec. 12, 2008, which claimspriority under 35 USC § 119(e) U.S. Provisional patent application Ser.No. 60/905,023, filed Mar. 5, 2007, the entire contents of which arehereby incorporated by reference.

TECHNICAL FIELD

The disclosure relates to embolic coils, as well as related methods anddevices.

BACKGROUND

Therapeutic vascular occlusions (embolizations) are used to prevent ortreat pathological conditions in situ. Embolic coils can be used toocclude vessles in a variety of medical applications. Delivery ofembolic coils (e.g., through a catheter) can depend on the size and/orshape of the coils. Some embolic coils include fibers that can, forexample, enhance thrombosis at the treatment site.

SUMMARY

In some systems, fibered coils can be placed in delivery catheters withfiber bundles oriented to facilitate delivery of the coil out of thecatheter. In some coils, the distribution of the fiber bundles along thecoils varies such that fiber bundle density, and thus column strength,is higher near the point at which deployment force is applied to thecoil.

In one aspect, a system includes a catheter having a delivery end; andan embolic coil at least partially disposed within the catheter. Theembolic coil includes a coil wires having an end fitting configured toreleasably couple to an end fitting of a delivery wire, and a fiberbundle contacting the catheter, the fiber bundle having a first bundleend being attached to the coil wire and a second bundle end opposite thefirst bundle end. The fiber bundle is disposed such that a distance fromthe first bundle end to the delivery end of the catheter is less than adistance from the second bundle end to the delivery end of the catheter.

In some embodiments, the embolic coil comprises multiple fiber bundlescontacting the catheter, each fiber bundle having first and secondbundle ends, the first bundle end being attached to the coil wire, thesecond bundle end opposite the first bundle end, the fiber bundle beingdisposed such that a distance from the first bundle end of a specificfiber bundle to the delivery end of the catheter is less than a distancefrom the second bundle end of the specific fiber bundle to the deliveryend of the catheter. In some cases, more fiber bundles are attached to afirst half of the coil than are attached to a second half of the coil.

In some embodiments, the coil is disposed in the catheter such that thesecond half of the coil is between the first half of the coil and thedelivery end of the catheter.

In some embodiments, spacing between adjacent fiber bundles increaseswith increasing distance from the end fitting of the coil wire.

In some embodiments, the fiber bundles are disposed in at least onegroup and the spacing between adjacent fiber bundles is constant withineach group of the at least one group.

In some embodiments, each fiber bundle is attached to the coil wire atan attachment point and a first attachment point is circumferentiallyspaced apart from a second attachment point. In some cases, theattachment point of each fiber bundle is circumferentially spaced apartfrom the attachment points of adjacent fiber bundles.

In some embodiments, the fiber bundle comprises polyethyleneterephthalate or nylon.

In some embodiments, wherein the coil wire has a diameter from 0.0075inch to 0.015 inch.

In some embodiments, wherein the fiber bundle has a length from 0.025inch to 0.125 inch.

In some embodiments, the coil wire comprises a metal.

In some embodiments, the system also includes a lubricant disposedwithin the catheter. In some cases, the lubricant is disposed on thefiber bundle.

In some embodiments, an inner surface of the catheter includes amaterial selected from the group consisting of polypropylene,polytetrafluoroethylene (PTFE), fluoroethylene polymer (FEP),low-density polyethylene (LDPE), high-density polyethylene (HDPE),nylon, Teflon®, and acrylic.

In one aspect, a coil includes: a coil wire having a first end, andopposite second end, and a midpoint located halfway between the firstend and the second end; and multiple fiber bundles attached to the coilwire. More fiber bundles are attached to the coil wire between the firstend and the midpoint than are attached to the coil wire between thesecond end and the midpoint. The coil is an embolic coil.

In some embodiments, spacing between adjacent fiber bundles increaseswith increasing distance from the first end of the coil.

In some embodiments, the fiber bundles are disposed in at least onegroup and the spacing between adjacent fiber bundles is constant withineach group of the at least one group.

In some embodiments, the coil also includes a end fitting attached tothe first end of the coil wire, the end fitting configured to releasablycouple the embolic coil to a mating end fitting of a delivery wire.

In some embodiments, a proximal end of the coil wire is configured toprovide an opposable surface configured for engagement of a pusherelement.

In one aspect, a system includes: a catheter having a delivery end; adelivery wire with an end fitting; and an embolic coil disposed withinthe catheter, the embolic coil having a first half and a second half,the second half disposed between the first half and the delivery end ofthe catheter, the embolic coil including a coil wire and multiple fiberbundles contacting the catheter, the coil wire having an end fittingconfigured to releasably couple to the end fitting of the delivery wireand each fiber bundle extending from a first bundle end attached to thecoil wire to a second bundle end opposite the first bundle end. Amajority of the fiber bundles are angled such that a distance from thefirst bundle end of a specific fiber bundle to the delivery end of thecatheter is less than a distance from the second bundle end of thespecific fiber bundle to the delivery end of the catheter. More fiberbundles are attached to the first half of the embolic coil than areattached to a second half of the coil.

In some embodiments, spacing between adjacent fiber bundles increaseswith increasing distance from the end fitting of the coil wire.

In some embodiments, the fiber bundles are disposed in groups and thespacing between adjacent fiber bundles is constant within each group.

In some embodiments, each fiber bundle is attached to the coil wire atan attachment point and a first attachment point is circumferentiallyspaced apart from a second attachment point. In some cases, theattachment point of each fiber bundle is circumferentially spaced apartfrom the attachment points of adjacent fiber bundles.

In one aspect, a method includes: advancing a delivery sheath over adistal end of an embolic coil while applying tension to the embolic coilvia a retaining device that is attached to the distal end of the emboliccoil.

In some embodiments, the method also includes engaging fiber bundlesextending from a first bundle end attached to the coil wire to a secondbundle end with the sheath such that, for a majority of the fiberbundles, a distance from the first bundle end of a specific fiber bundleto a proximal end fitting of the embolic coil is greater than a distancefrom the second bundle end of the specific fiber bundle to the endfitting of the embolic coil. In some cases, the method also includesstopping advancement of the sheath after the distal end of the coilemerges from a delivery end of the sheath and before any of the fiberbundles emerge from the delivery end of the sheath. In some cases, themethod also includes detaching the retaining device from the distal endof the coil. In some cases, the method also includes refining the distalend of the coil. In some cases, the method also includes withdrawing thedistal end of the coil into the sheath.

In some embodiments, the method also includes stopping advancement ofthe catheter over the embolic coil before a proximal end of the coilenters the sheath. In some cases, the method also includes engaging anend fitting of a delivery wire with a proximal end fitting of the coil.

In some embodiments, the coils can exhibit relatively little frictionduring deployment.

In certain embodiments, the coils exhibit relatively high columnstrength near the point of application of deployment force at theproximal end of the coil.

Other features and advantages will be apparent from the description,drawings, and claims.

DESCRIPTION OF DRAWINGS

FIGS. 1A-1C are a cross-sectional views of an embodiment of an emboliccoil delivery system before, during, and after delivery of an emboliccoil.

FIG. 2 is a cross-sectional view of an embodiment of an embolic coildelivery system.

FIG. 3 is a cross-sectional view of an embodiment of an embolic coildelivery system.

FIG. 4 is a cross-sectional view of an embodiment of an embolic coildelivery system.

FIGS. 5A and 5B are, respectively, perspective and end views of anembodiment of an embolic coil.

FIG. 6 is a schematic view of an embodiment of a process for forming anembolic coil.

FIG. 7A is a side view of an embodiment of a mandrel.

FIGS. 7B and 7C illustrate an embodiment of a process for forming anembolic coil using the mandrel of FIG. 7A.

FIGS. 8A-8H are a perspective views embodiments of embolic coils.

FIG. 9 is a schematic view of an embodiment of a process for loading anembolic coil into a catheter.

FIG. 10 is a cross-sectional view of an embodiment of an embolic coildelivery system.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

Embolic coils can be used for purposes including, for example, to closeblood vessels and/or fill aneurysmal sacs. Fibered embolic coils caninclude thrombogenic fiber bundles attached to the coil at prescribedintervals to enhance coil thrombosis. Detachable coils include apre-attached delivery system (typically a wire) for delivery of the coilto the desired site. Upon completion of satisfactory positioning, theembolic coil is detached from the delivery system. Pushable coils arenot attached to the delivery system but rather are pushed by wire-likedevices for one-way deployment.

FIGS. 1A-1C show the use of an embolic coil delivery system 100 todeliver a detachable embolic coil 110 to fill and occlude an aneurysmalsac 134. Embolic coil delivery system 100 includes an embolic coil 110disposed within a catheter 112. Embolic coil 110 is detachably engagedto delivery wire 111 which extends proximally out of catheter 112. Insome embodiments, embolic coil 110 can be disposed within a carrierfluid (e.g., a saline solution, a contrast agent, a heparin solution)while embolic coil 110 is within catheter 112. In FIG. 1B, catheter 112is delivered into a lumen 128 of a subject. An end fitting 130 ofembolic coil 110 is detachably engaged with an end fitting 132 ofdelivery wire 111. The end fittings 130, 132 can be maintained inengagement with each other while coil 110 is in catheter 112 becausethere is insufficient clearance in catheter 112 for them to disengage.Delivery wire 111 is used to push embolic coil 110 out of catheter 112through delivery end 126 of catheter 112, into lumen 128, and toward ananeurysmal sac 134 formed in wall 136 of lumen 128. FIG. 1C showsembolic coil 110 filling aneurysmal sac 134 after embolic coil 110 hasbeen pushed out of catheter 112 and disengaged from delivery wire 111.By filling aneurysmal sac 134, embolic coil 110 helps to occludeaneurysmal sac 134. This occlusion of aneurysmal sac 134 can beaccelerated by fiber bundles 116, which can enhance thrombosis withinaneurysmal sac 134. An accelerated embolization procedure can benefitthe subject by, for example, reducing exposure time to fluoroscopy.

Detachable embolic coils are described, for example, in Twyford, Jr. etal., U.S. Pat. No. 5,304,195; Guglielmi et al., U.S. Pat. No. 5,895,385;and Buiser et al., U.S. patent application Ser. No. 11/311,617, filed onDec. 19, 2005, and entitled “Coils”.

Embolic coil 110 includes a coil wire 114. In some embodiments, coilwire 114 is wound in a spiral configuration. Fiber bundles 116 extendfrom coil wire 114 into contact with inner surfaces 118 of catheter 112such that the fibers in fiber bundles 116 are axially deflected. Ingeneral, fiber bundles 116 include multiple fibers extending from asingle attachment point as shown. However, in some embodiments, a singlefiber can make up a fiber bundle.

The fiber bundles 116 can have a length L₁ that exceeds a radialdistance d between coil wire 114 and inner surfaces 118 of catheter 112.For example, one embodiment of an embolic coil delivery system includesan embolic coil wire portion with an outer diameter OD of 0.012 inch, acatheter with an inner diameter ID of 0.021 inch, and fiber bundles 116with a length L₁ of 0.079 inch. As will be described in more detailbelow, embolic coil 110 is loaded into catheter 112 such that fiberbundles 116 extend from their point of attachment to coil wire 114 awayfrom delivery end 126 of catheter 112. For example, in the embodimentshown in FIGS. 1A and 1B, a first end 122 of fiber bundle 116 isattached to coil wire 114. Fiber bundle 116 contacts inner surface 118of catheter 112 and extends away from delivery end 126 of catheter 112to second end 124 of fiber bundle 116 (e.g., a distance L₂ from firstbundle end 122 to delivery end 126 of catheter 112 is less than adistance L₃ from second bundle end 124 to delivery end 126 of thecatheter 112). In some embodiments, an inner surface 118 of catheter 112comprises a material with a coefficient of friction below about 0.3(e.g., polypropylene, polytetrafluoroethylene (PTFE), fluoroethylenepolymer (FEP), low-density polyethylene (LDPE), high-densitypolyethylene (HDPE), nylon, Teflon®, acrylic).

In some cases, during delivery, thrombus can begin to build up onembolic coil 110 within catheter 112. The configuration of fiber bundles116 as described above can reduce friction between embolic coil 110 andcatheter 112 during deployment of embolic coil 110, which, in turn, canreduce the possibility that coil 110 will undesirably buckle duringdelivery.

Coil wire 114 includes windings 138 and 140. In general, there is littleto no space between consecutive windings (e.g., windings 138 and 140) ofembolic coil 110. As a result, fiber bundles 116 are generally tightlyfitted between consecutive windings of embolic coil 110.

The pitch of an embolic coil is the sum of the thickness of one windingof coil wire 114 (e.g., winding 138) and the amount of space betweenthat winding and a consecutive winding (e.g., winding 140). In someembodiments, embolic coil 110 can have a pitch of at most about 0.01inch (e.g., about 0.003 inch). Because the windings of embolic coil 110are flush with each other, the pitch of embolic coil 110 is equal to thediameter of coil wire 114.

The diameter of coil wire 114 can be selected, for example, based on thedesired properties (e.g., size, strength) and/or applications of emboliccoil 110. In some embodiments, coil wire 114 can have a diameter of from0.001 inch to 0.005 inch (e.g., from 0.0015 inch to 0.005 inch, from0.002 inch to 0.003 inch, from 0.00225 inch to 0.003 inch). In certainembodiments, coil wire 114 can have a diameter of 0.003 inch. In someembodiments (e.g., embodiments in which embolic coil 110 is used forperipheral vascular applications), coil wire 114 can have a diameter ofat least about 0.004 inch. In certain embodiments (e.g., embodiments inwhich embolic coil 110 is used for neurological applications), coil wire114 can have a diameter of at most about 0.002 inch. Alternatively oradditionally, coil wire 114 can have a restrained length of at mostabout 50 centimeters (e.g., at most about 40 centimeters, at most about30 centimeters, at most about 20 centimeters).

Coil wire 114 can be formed of, for example, one or more metals or metalalloys, such as platinum, a platinum alloy (e.g., a platinum-tungstenalloy), stainless steel, nitinol, and Elgiloy® (from Elgiloy SpecialtyMetals). Embolic coils can be formed from wires with a roundcross-section (see FIGS. 1A-1C) or from wires with other cross sections(e.g., ribbon-shaped wires; see FIGS. 5A and 5B).

Fiber bundles 116 are typically formed of one or more materials that canenhance thrombosis (e.g., at a target site). Examples of materials fromwhich fiber bundles 116 can be made include polyethylene terephthalate(e.g., Dacron®), nylon, and collagen. Fibers can be made from materialswith a coefficient of friction below about 0.35. Fiber bundles 116 canhave a length of from about 0.5 millimeter to about five millimeters(e.g., about 2.5 millimeters).

Embolic coils can generally be used in a number of differentapplications, such as neurological application and/or peripheralapplications. In some embodiments, embolic coils can be used to occludea vessel, and/or to treat an aneurysm (e.g., an intercranial aneurysm),an arteriovenous malformation (AVM), or a traumatic fistula. In someembodiments, embolic coils can be used to embolize a tumor (e.g., aliver tumor). In certain embodiments, embolic coils can be used intransarterial chemoembolization (TACE).

Fibered embolic coils can have fiber bundle distributions that aresubstantially uniform along the length of the coils (see FIGS. 1A-1C).However, fibered embolic coils can also have fiber bundle distributionsthat vary along the length of the coils such that the fiber density(e.g., fiber bundles per unit length of the coil) is greater in someportions of the coils that in other portions of the coils. For example,there can be more fiber bundles attached to a proximal half of theembolic coil than are attached to a distal half of embolic coil. In someinstances, the distribution of fiber bundles in an embolic coil canaffect the structural properties of the coil.

In some embodiments, the presence of fiber bundles can increase thecolumn strength of a first section of an embolic coil where fiberbundles are present relative to a second section of the embolic coilwhere fewer (e.g., none) fiber bundles are present. For example, bylocating the first section proximally of the second section, a proximalhalf of the embolic coil can include more fiber bundles than a distalhalf of the embolic coil. Increasing the fiber density of embolic coilnear a proximal end of the embolic coil where a pusher wire contacts theembolic coil can concentrate sources of friction (e.g., fiber bundlesand associated thrombus) near the location at which the delivery forceis applied. In some cases, this can reduce the likelihood of a jammedcoil.

FIG. 2 shows an embodiment of an embolic coil delivery system 200 whichincludes a embolic coil 210 with a fiber bundle distribution that variesalong the length of coil 210. Embolic coil 210 is disposed withincatheter 211. Fiber bundles 212 are attached to a coil wire 214 ofembolic coil 210 in a first section 216 of the embolic coil. A secondsection 218 of embolic coil 210 is free of fiber bundles 212. In thisembodiment, fiber bundles 212 are disposed in a single group in whichthe spacing S between first ends of adjacent fiber bundles 212 isconstant within the group. An end fitting 224 of coil 210 is disposed ata first end 221 of coil 210 to configure first end 221 for engagementwith delivery wire 225. A midpoint 219 of coil 210 lies halfway betweenfirst end 221 and an opposite second end 223. In this embodiment, fiberbundles 212 are disposed on a portion of proximal half 220 of coil 210between first end 221 and midpoint 219. No fiber bundles 212 are presenton distal half 222 of coil 210 between midpoint 219 and second end 223.

Other distributions are also possible. In this embolic coil deliverysystem 200, fiber bundles 212 are evenly distributed within the firstsection 216 of embolic coil 210. However, in some embodiments, the fiberdensity of embolic coils can vary within the sections where fiberbundles are present. For example, in some embodiments, the spacingbetween adjacent fiber bundles increases with increasing distance from aproximal end of the coil.

FIG. 3 shows an embodiment of an embolic coil delivery system 300 whichincludes a embolic coil 310 with multiple groups G₁, G₂ of fiber bundles312. In this embodiment, fiber bundles 312 in a first group G₁ havespacing S₁ between first ends 328 of adjacent fiber bundles 312. Fiberbundles 312 in a second group G₂ have spacing S₂, which is greater thanS₁, between first ends 328 of adjacent fiber bundles 312.

FIG. 4 shows an embodiment of an embolic coil delivery system 400 whichincorporates another variable fiber bundle distribution. Embolic coildelivery system 400 includes an embolic coil 410 disposed within acatheter 412. First ends 413 of fiber bundles 414 are attached to wire416 of embolic coil 410. The spacing between first ends 413 of adjacentfiber bundles 414 increases with increasing distance from an end fitting424 of coil 410 is disposed at a first end 421 of coil 410 to configurefirst end 421 for contact with delivery wire 425 (e.g.,S₁<S₂<S₃<S₄<S₅<S₆). A midpoint 419 of coil 410 lies halfway betweenfirst end 421 and an opposite second end 423. In this embodiment, fiberbundles 412 are disposed in both a proximal half 420 of coil 410 (e.g.,between first end 421 and midpoint 419) and in a distal half 422 of coil410 (e.g., between midpoint 419 and second end 423). However, more fiberbundles 414 are present in proximal half 420 of coil 410 than in distalhalf 422 of the coil 410.

FIGS. 5A and 5B show an embolic coil 500 with fiber bundles 502 whoseattachment points are offset from each around the circumference of coil502. Embolic coil 500 includes a ribbon-shaped coil wire 504 with fiberbundles 502 inserted between windings of coil wire 504. In thisembodiment, the attachment point of each fiber bundle 502 iscircumferentially spaced apart from the attachment points of adjacentfiber bundles (e.g., viewed looking down the axis of coil 500, linesdrawn from the axis to the attachment point of adjacent fiber bundleswould appear to form an angle). Other arrangements are also possible.For example, in some embodiments, some (e.g., at least two) fiberbundles have attachment points which are offset from each other whileother fiber bundles have attachment points which are axially alignedwith each other.

In some embodiments, embolic coil delivery systems include a lubricantcoating. For example, some embolic coil delivery systems include alubricant coating disposed on at least some of fiber bundles. Someembolic coil delivery systems include a lubricant coating disposed on aninner surface of a delivery catheter. Some embolic coil delivery systemsinclude a lubricant coating disposed both on an inner surface of adelivery catheter and on fiber bundles of the embolic coil beingdelivered. Lubricant coatings can be applied to fiber bundles and/or canbe applied to the interior surfaces of delivery catheters before theembolic coils are inserted into the catheters. Lubricant coatings caninclude a polymer coating, a bioerodible material, a bioabsorbablematerial and/or other appropriate materials. In some instances,lubricant coatings can reduce friction between embolic coils andcatheters. In some instances, lubricious coatings can act to reducethrombosis in catheters. Coatings for embolic coils are discussed inmore detail in Buiser et al., U.S. patent application Ser. No.11/458,156, filed on Jul. 18, 2006 which is incorporated herein byreference.

In general, embolic coils have a primary shape and a secondary shape.Embolic coils exhibit their primary shapes when the embolic coils arefully extended within a catheter (as shown in FIGS. 1B, 2, and 3 ). Asembolic coils exit the delivery catheter, however, embolic coils furtherassume their secondary shapes (as shown in FIG. 1C), which allow theembolic coils to fill, for example, an aneurysmal sac. Typically, theprimary shape of embolic coils are selected for deliverability, and thesecondary shapes of embolic coils are selected for application (e.g.,embolization of an aneurysm).

FIG. 6 shows a coil-forming apparatus 600 that can be used to form anembolic coil 612 in its primary shape. Coil-forming apparatus 600includes a mandrel 610 held by two rotatable chucks 620 and 630. A spool640 of wire 617 is disposed above mandrel 610, and is attached to alinear drive 660. To form an embolic coil in its primary shape, chucks620 and 630 are activated so that they rotate in the direction of arrowsA2 and A3, thereby rotating mandrel 610. Linear drive 660 also isactivated, and moves spool 640 in the direction of arrow A1. Therotation of mandrel 610 pulls wire 617 from spool 640 at a predeterminedpull-off angle (alpha) α, and causes wire 617 to wrap around mandrel610, forming embolic coil body 612. The pull-off angle (alpha) α is theangle between axis PA1, which is perpendicular to longitudinal axis LA1of mandrel 610, and the portion 680 of wire 617 between spool 640 andembolic coil body 612. In some embodiments, α can be from about onedegree to about six degrees (e.g., from about 1.5 degrees to about fivedegrees, from about 1.5 degrees to about 2.5 degrees, about twodegrees). In certain embodiments, a controller (e.g., a programmablelogic controller) can be used to maintain the pull-off angle (alpha) αin coil-forming apparatus 600. Because mandrel 610 is rotating as it ispulling wire 617 from spool 640, and because linear drive 660 is movingspool 640 in the direction of arrow A1, wire 617 forms embolic coil body612 in a primary shape around mandrel 610. Embolic coil body 612 can beformed, for example, at room temperature (25° C.).

After embolic coil body 612 has been formed, chucks 620 and 630, andlinear drive 660, are deactivated, and portion 680 of wire 617 is cut.Mandrel 610 is then released from chuck 620, and embolic coil body 612is pulled off of mandrel 610. While embolic coil body 612 might losesome of its primary shape as it is pulled off of mandrel 610, emboliccoil body 612 can generally return to its primary shape shortlythereafter, because of memory imparted to embolic coil body 612 duringformation. In some embodiments, after embolic coil body 612 has beenremoved from mandrel 610, one or both of the ends of embolic coil body612 can be heated and melted to form rounder, more biocompatible (e.g.,atraumatic) ends. In some embodiments, end fittings can be attached toone or both ends of embolic coil body 612 (e.g., to form a detachableembolic coil).

The tension of mandrel 610 as it is held between chucks 620 and 630preferably is sufficiently high to avoid vibration of mandrel 610 duringthe winding process, and sufficiently low to avoid stretching of mandrel610 during the winding process. In some instances, significantstretching of mandrel 610 during the winding process could cause emboliccoil body 612 to have a smaller primary shape than desired, and/or couldmake it relatively difficult to remove embolic coil body 612 frommandrel 610.

In certain embodiments, the length of embolic coil body 612 in itsprimary shape and while under tension on mandrel 610 can be from about10 centimeters to about 250 centimeters (e.g., from about 50 centimetersto about 200 centimeters, from about 130 centimeters to about 6170centimeters, from about 144 centimeters to about 153 centimeters, fromabout 147 centimeters to about 153 centimeters). For example, the lengthof embolic coil body 612 in its primary shape and while under tension onmandrel 610 can be about 132 centimeters or about 147 centimeters.Embolic coil body 612 may recoil to some extent (e.g., by at most aboutfive centimeters) when portion 680 of wire 617 is severed, such thatembolic coil body 612 will be somewhat smaller once it has been removedfrom mandrel 610. In some embodiments, embolic coil body 612 can have alength of from about five centimeters to about 225 centimeters (e.g.,from about 25 centimeters to about 6170 centimeters, from about 6120centimeters to about 140 centimeters, from about 137 centimeters toabout 140 centimeters) after being removed from mandrel 610. Afterembolic coil body 612 has been removed from mandrel 610, embolic coilbody 612 can be cut into smaller coils.

Once embolic coil wire 612 has been formed in its primary shape, emboliccoil wire 612 can be further shaped into a secondary shape, as shown inFIGS. 7A-7C.

FIG. 7A shows a mandrel 790 used to form a secondary shape of emboliccoil wire 612. While mandrel 790 is shaped to form a diamond (also knownas a double vortex), other types of mandrels can be used to form othersecondary shapes. Mandrel 790 is formed of a diamond-shaped block 792with grooves 794 cut into its surface. As shown in FIGS. 7B and 7C,embolic coil wire 612 in its primary shape is wrapped around mandrel790, such that embolic coil wire 612 fills grooves 794, creating thesecondary shape. The ends of embolic coil wire 612 are then attached(e.g., pinned) to mandrel 790, and embolic coil wire 612 is heat-treatedto impart memory to coil wire 612. In some embodiments, embolic coilwire 612 can be heat-treated at a temperature of at least about 1000° F.(e.g., at least about 1050° F., at least about 1100° F., at least about1150° F.), and/or at most about 1300° F. (e.g., at most about 1150° F.,at most about 1100° F., at most about 1050° F.). In certain embodiments,the heat treatment of embolic coil wire 612 can last for a period offrom about 10 minutes to about 150 minutes (e.g., about 25 minutes)including ramp and dwell time. After being heat-treated, embolic coilwire 612 is unwrapped from mandrel 790. The removal of embolic coil wire612 from mandrel 790 allows embolic coil wire 612 to reassume itssecondary shape. In some embodiments, after embolic coil wire 612 hasbeen removed from mandrel 790, one or both of the ends of embolic coilwire 612 can be heated and melted to form rounder, more atraumatic ends.

Mandrel 790 can be formed of, for example, a metal or a metal alloy(e.g., stainless steel). In some embodiments, mandrel 790 can be formedof a plated metal or a plated metal alloy (e.g., chrome-plated stainlesssteel).

After embolic coil wire 612 has been removed from mandrel 790, fiberbundles can be attached to embolic coil wire 612. In certainembodiments, embolic coil wire 612 can be stretched prior to attachingfiber bundles, so that embolic coil wire 612 is in its primary shape,and can then be loaded onto a fibering mandrel (e.g., a fibering mandrelfrom Sematool Mold and Die Co., Santa Clara, Calif.). In someembodiments, fiber bundles can be attached to embolic coil wire 612 bytying the fiber bundles to wire 617 of embolic coil wire 612, wrappingthe fiber bundles around wire 617, and/or snapping the fiber bundles inbetween windings of wire 617. In certain embodiments, one portion (e.g.,one end) of a bunch of fiber bundles can be snapped in between windingsin one region of embolic coil wire 612, and another portion (e.g., theother end) of the same bunch of fiber bundles can be wrapped around partof embolic coil wire 612 and snapped in between windings in anotherregion of embolic coil wire 612. In some embodiments, fiber bundles canbe attached to embolic coil wire 612 by bonding (e.g., adhesive bonding)the fiber bundles to wire 617 of embolic coil wire 612.

Exemplary secondary shapes are illustrated in FIGS. 8A-8H. For example,FIG. 8A shows an embolic coil 500 with a spiral secondary shape, whichcan be used, e.g., to provide a supportive framework along a vessel walland/or to hold other embolic coils that are subsequently delivered tothe target site. FIG. 8B shows an embolic coil 502 with vortex orconical secondary shape, which can be used, e.g., to close the center ofa target site such as a vessel or an aneurysm that is to be occluded,optionally in conjunction with an embolic coil or coils, for example, acoil of a different secondary shape. As shown in FIG. 8C, embolic coil504 can have a diamond secondary shape which can be utilized in afashion similar to coil 502. FIG. 8D shows a dual-spiral secondary shape505 in which two conical shapes 506 and 507 meet at their smaller ends.FIG. 8E shows an embolic coil 508 with secondary shape in the form of aJ, which can be used, for example, to fill remaining space in ananeurysm not filled by other coils. Optionally, a curved portion 509 ofembolic coil 508 can be hooked by the operator (e.g., a physician) intoa coil or coil mass that has already been deployed at the target site,with a straight part 510 of embolic coil 508 optionally extending intoopen space to fill the target site. FIG. 8F shows an embolic coil 512with a secondary shape in the form of a spiral having a first section514 with a first helical diameter and a second section 516 with a secondhelical diameter. Such a coil can be used, for example, to provide asupportive framework along a vessel wall and simultaneously occlude orpartially occlude the vessel and/or hold other embolic coils that aresubsequently delivered to the target site. FIG. 8G shows an embolic coil518 having a basket-shaped secondary shape, which can be used, forexample, to frame an aneurysm and/or hold or provide a support for otherembolic coils that are subsequently delivered to the target site. Any ofthe shapes just described can be achieved using a braided embolic coil;for example, FIG. 8H shows a braided embolic coil 520 having a secondaryshape in the form of a C, which may be used, e.g., in filling ananeurysm. It should be noted that these secondary shapes areapproximations, and that the coils may be, for example, a diamond-shapeor substantially a diamond shape. Other secondary shapes include randomor tangled, generally spherical or spheroid, generally elliptical,clover-shaped, box-shaped. Also included are three-dimensional shapessuch as these in which a single coil frames the shape and fills orpartially fills the shape. For example, a spherical-shaped coil couldhave a generally spherical coil frame and be partially filled by thesame coil that forms the frame.

Referring to FIG. 9 , to load a coil 900 into the introducer sheath 902such that the fiber bundles are oriented as described above, a “donor”wire 904 is attached via a crimping process to a distal end 906 of coil900 and is used to pull or slide coil 900 through sheath 902 in thedistal direction. In this embodiment of the method, sheath 902 isclamped into movable carriages 908. Donor wire 904 is clamped in placeto fix the position of coil 900 while movable carriages 908 pull sheath902 over coil 900. When just a coil arm 910 is protruding out of theproximal end 912 of sheath 902, an interlocking arm 914 of coil 900 ismanually attached to the interlocking arm of a pusher wire 916.Continued movement of sheath 902 causes donor wire 904, coil 900, andpusher wire 916 to continue to advance through sheath 902 in the distaldirection until distal end 906 of coil 900 is just protruding through adistal end 918 of sheath 902. Donor wire 904 is trimmed from coil 900and coil 900 is “zapped” or electrically fused to create an atraumaticend. Pusher wire 916 is pulled back in the proximal direction untildistal end 906 of coil 900 sits approximately 1-2 centimeters back fromdistal end 918 of sheath 902. This is necessary for fibered detachablecoils because it allows for the fiber orientation to be in the antegradedirection (delivery direction) within the sheath for ease of delivery(i.e. minimal friction) as discussed above.

In some embodiments, an embolic coil such as an embolic coil can includeone or more therapeutic agents (e.g., drugs). For example, an emboliccoil wire, fiber bundles, and/or a coating of an embolic coil caninclude one or more therapeutic agents. Embolic coil can, for example,be used to deliver the therapeutic agents to a target site.

In certain embodiments, one component of embolic coil (e.g., emboliccoil body) can include one or more therapeutic agents that are the sameas, or different from, one or more therapeutic agents in a coating. Insome embodiments, therapeutic agents can be dispersed within thecoating. In certain embodiments, the coating can contain a therapeuticagent (e.g., heparin) that limits or prevents thrombosis. When thecoating is eroded and/or absorbed, thereby releasing the therapeuticagent into the body of the subject (e.g., during delivery), thetherapeutic agent can limit or prevent premature thrombosis.

In some embodiments, an embolic coil can include one or more therapeuticagents that are coated onto an embolic coil wire and/or that areincluded in a coating. In some embodiments, a therapeutic agent can becompounded with a polymer that is included in a coating. In certainembodiments, a therapeutic agent can be applied to the surface of anembolic coil wire and/or to a coating by exposing the embolic coil wireand/or coating to a high concentration solution of the therapeuticagent.

In some embodiments, a therapeutic agent-coated embolic coil can includea coating (e.g., a bioerodible and/or bioabsorbable polymer coating)over the surface the therapeutic agent. The coating can assist incontrolling the rate at which therapeutic agent is released from theembolic coil. For example, the coating can be in the form of a porousmembrane. The coating can delay an initial burst of therapeutic agentrelease. The coating can be applied by dipping or spraying the emboliccoil. The coating can include therapeutic agent or can be substantiallyfree of therapeutic agent. The therapeutic agent in the coating can bethe same as or different from an agent on a surface layer of the emboliccoil body, and/or in a coating on the embolic coil body, and/or withinthe embolic coil body. A polymer coating (e.g., that is bioerodibleand/or bioabsorbable) can be applied to an embolic coil body surfaceand/or to a coated embolic coil surface in embodiments in which a highconcentration of therapeutic agent has not been applied to the emboliccoil body surface or to the coated coil surface.

Coatings are described, for example, in DiMatteo et al., U.S. patentapplication Publication No. U.S. 2004/0076582 A1, published on Apr. 22,2004, and entitled “Agent Delivery Particle”, which is incorporatedherein by reference.

In some embodiments, one or more embolic coils can be disposed in atherapeutic agent that can serve as a pharmaceutically acceptablecarrier.

Therapeutic agents include genetic therapeutic agents, non-genetictherapeutic agents, and cells, and can be negatively charged, positivelycharged, amphoteric, or neutral. Therapeutic agents can be, for example,materials that are biologically active to treat physiologicalconditions; pharmaceutically active compounds; gene therapies; nucleicacids with and without carrier vectors (e.g., recombinant nucleic acids,DNA (e.g., naked DNA), cDNA, RNA, genomic DNA, cDNA or RNA in anon-infectious vector or in a viral vector which may have attachedpeptide targeting sequences, antisense nucleic acids (RNA, DNA));peptides (e.g., growth factor peptides, such as basic fibroblast growthfactor (bFGF)); oligonucleotides; gene/vector systems (e.g., anythingthat allows for the uptake and expression of nucleic acids); DNAchimeras (e.g., DNA chimeras which include gene sequences and encodingfor ferry proteins such as membrane translocating sequences (“MTS”) andherpes simplex virus-1 (“VP22”)); compacting agents (e.g., DNAcompacting agents); viruses; polymers; hyaluronic acid; proteins (e.g.,enzymes such as ribozymes, asparaginase); immunologic species;nonsteroidal anti-inflammatory medications; chemoagents; pain managementtherapeutics; oral contraceptives; progestins; gonadotrophin-releasinghormone agonists; chemotherapeutic agents; and radioactive species(e.g., radioisotopes, radioactive molecules). Non-limiting examples oftherapeutic agents include anti-thrombogenic agents; antioxidants;angiogenic and anti-angiogenic agents and factors; anti-proliferativeagents (e.g., agents capable of blocking smooth muscle cellproliferation); calcium entry blockers; and survival genes which protectagainst cell death (e.g., anti-apoptotic Bcl-2 family factors and Aktkinase).

Exemplary non-genetic therapeutic agents include: anti-thrombotic agentssuch as heparin, heparin derivatives, urokinase, and PPack(dextrophenylalanine proline arginine chloromethylketone);anti-inflammatory agents such as dexamethasone, prednisolone,corticosterone, budesonide, estrogen, acetyl salicylic acid,sulfasalazine and mesalamine;antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel,5-fluorouracil, cisplatin, methotrexate, doxorubicin, vinblastine,vincristine, epothilones, endostatin, angiostatin, angiopeptin,monoclonal antibodies capable of blocking smooth muscle cellproliferation, and thymidine kinase inhibitors; anesthetic agents suchas lidocaine, bupivacaine and ropivacaine; anti-coagulants such asD-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound,heparin, hirudin, antithrombin compounds, platelet receptor antagonists,anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin,prostaglandin inhibitors, platelet inhibitors and tick antiplateletfactors or peptides; vascular cell growth promoters such as growthfactors, transcriptional activators, and translational promoters;vascular cell growth inhibitors such as growth factor inhibitors (e.g.,PDGF inhibitor-Trapidil), growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bifunctional molecules consisting of a growth factor and acytotoxin, bifunctional molecules consisting of an antibody and acytotoxin; protein kinase and tyrosine kinase inhibitors (e.g.,tyrphostins, genistein, quinoxalines); prostacyclin analogs;cholesterol-lowering agents; angiopoietins; antimicrobial agents such astriclosan, cephalosporins, aminoglycosides and nitrofurantoin; cytotoxicagents, cytostatic agents and cell proliferation affectors; vasodilatingagents; and agents that interfere with endogenous vasoactive mechanisms.

Exemplary genetic therapeutic agents include: anti-sense DNA and RNA;DNA coding for anti-sense RNA, tRNA or rRNA to replace defective ordeficient endogenous molecules, angiogenic factors including growthfactors such as acidic and basic fibroblast growth factors, vascularendothelial growth factor, epidermal growth factor, transforming growthfactor α and β, platelet-derived endothelial growth factor,platelet-derived growth factor, tumor necrosis factor a, hepatocytegrowth factor, and insulin like growth factor, cell cycle inhibitorsincluding CD inhibitors, thymidine kinase (“TK”) and other agents usefulfor interfering with cell proliferation, and the family of bonemorphogenic proteins (“BMP's”), including BMP2, BMP3, BMP4, BMP5, BMP6(Vgr1), BMP7 (OP1), BMP8, BMP9, BMP10, BM11, BMP12, BMP13, BMP14, BMP15,and BMP16. Currently preferred BMP's are any of BMP2, BMP3, BMP4, BMP5,BMP6 and BMP7. These dimeric proteins can be provided as homodimers,heterodimers, or combinations thereof, alone or together with othermolecules. Alternatively or additionally, molecules capable of inducingan upstream or downstream effect of a BMP can be provided. Suchmolecules include any of the “hedgehog” proteins, or the DNA's encodingthem. Vectors of interest for delivery of genetic therapeutic agentsinclude: plasmids; viral vectors such as adenovirus (AV),adenoassociated virus (AAV) and lentivirus; and non-viral vectors suchas lipids, liposomes and cationic lipids.

Cells include cells of human origin (autologous or allogeneic),including stem cells, or from an animal source (xenogeneic), which canbe genetically engineered if desired to deliver proteins of interest.

Several of the above and numerous additional therapeutic agentsappropriate for the practice of the present invention are disclosed inKunz et al., U.S. Pat. No. 5,733,925, assigned to NeoRx Corporation,which is incorporated herein by reference. Therapeutic agents disclosedin this patent include the following: “Cytostatic agents” (i.e., agentsthat prevent or delay cell division in proliferating cells, for example,by inhibiting replication of DNA or by inhibiting spindle fiberformation). Representative examples of cytostatic agents includemodified toxins, methotrexate, adriamycin, radionuclides (e.g., such asdisclosed in Fritzberg et al., U.S. Pat. No. 4,897,255), protein kinaseinhibitors, including staurosporin, a protein kinase C inhibitor of thefollowing formula:

as well as diindoloalkaloids having one of the following generalstructures:

as well as stimulators of the production or activation of TGF-beta,including Tamoxifen and derivatives of functional equivalents (e.g.,plasmin, heparin, compounds capable of reducing the level orinactivating the lipoprotein Lp(a) or the glycoproteinapolipoprotein(a)) thereof, TGF-beta or functional equivalents,derivatives or analogs thereof, suramin, nitric oxide releasingcompounds (e.g., nitroglycerin) or analogs or functional equivalentsthereof, paclitaxel or analogs thereof (e.g., taxotere), inhibitors ofspecific enzymes (such as the nuclear enzyme DNA topoisomerase II andDNA polymerase, RNA polymerase, adenyl guanyl cyclase), superoxidedismutase inhibitors, terminal deoxynucleotidyl-transferase, reversetranscriptase, antisense oligonucleotides that suppress smooth musclecell proliferation and the like. Other examples of “cytostatic agents”include peptidic or mimetic inhibitors (i.e., antagonists, agonists, orcompetitive or non-competitive inhibitors) of cellular factors that may(e.g., in the presence of extracellular matrix) trigger proliferation ofsmooth muscle cells or pericytes: e.g., cytokines (e.g., interleukinssuch as IL-1), growth factors (e.g., PDGF, TGF-alpha or -beta, tumornecrosis factor, smooth muscle- and endothelial-derived growth factors,i.e., endothelin, FGF), homing receptors (e.g., for platelets orleukocytes), and extracellular matrix receptors (e.g., integrins).Representative examples of useful therapeutic agents in this category ofcytostatic agents addressing smooth muscle proliferation include:subfragments of heparin, triazolopyrimidine (trapidil; a PDGFantagonist), lovastatin, and prostaglandins E1 or I2.

Agents that inhibit the intracellular increase in cell volume (i.e., thetissue volume occupied by a cell), such as cytoskeletal inhibitors ormetabolic inhibitors. Representative examples of cytoskeletal inhibitorsinclude colchicine, vinblastin, cytochalasins, paclitaxel and the like,which act on microtubule and microfilament networks within a cell.Representative examples of metabolic inhibitors include staurosporin,trichothecenes, and modified diphtheria and ricin toxins, Pseudomonasexotoxin and the like. Trichothecenes include simple trichothecenes(i.e., those that have only a central sesquiterpenoid structure) andmacrocyclic trichothecenes (i.e., those that have an additionalmacrocyclic ring), e.g., a verrucarins or roridins, including VerrucarinA, Verrucarin B, Verrucarin J (Satratoxin C), Roridin A, Roridin C,Roridin D, Roridin E (Satratoxin D), Roridin H.

Agents acting as an inhibitor that blocks cellular protein synthesisand/or secretion or organization of extracellular matrix (i.e., an“anti-matrix agent”). Representative examples of “anti-matrix agents”include inhibitors (i.e., agonists and antagonists and competitive andnon-competitive inhibitors) of matrix synthesis, secretion and assembly,organizational cross-linking (e.g., transglutaminases cross-linkingcollagen), and matrix remodeling (e.g., following wound healing). Arepresentative example of a useful therapeutic agent in this category ofanti-matrix agents is colchicine, an inhibitor of secretion ofextracellular matrix. Another example is tamoxifen for which evidenceexists regarding its capability to organize and/or stabilize as well asdiminish smooth muscle cell proliferation following angioplasty. Theorganization or stabilization may stem from the blockage of vascularsmooth muscle cell maturation in to a pathologically proliferating form.

Agents that are cytotoxic to cells, particularly cancer cells. Preferredagents are Roridin A, Pseudomonas exotoxin and the like or analogs orfunctional equivalents thereof. A plethora of such therapeutic agents,including radioisotopes and the like, have been identified and are knownin the art. In addition, protocols for the identification of cytotoxicmoieties are known and employed routinely in the art.

A number of the above therapeutic agents and several others have alsobeen identified as candidates for vascular treatment regimens, forexample, as agents targeting restenosis. Such agents include one or moreof the following: calcium-channel blockers, including benzothiazapines(e.g., diltiazem, clentiazem); dihydropyridines (e.g., nifedipine,amlodipine, nicardapine); phenylalkylamines (e.g., verapamil); serotoninpathway modulators, including 5-HT antagonists (e.g., ketanserin,naftidrofuryl) and 5-HT uptake inhibitors (e.g., fluoxetine); cyclicnucleotide pathway agents, including phosphodiesterase inhibitors (e.g.,cilostazole, dipyridamole), adenylate/guanylate cyclase stimulants(e.g., forskolin), and adenosine analogs; catecholamine modulators,including α-antagonists (e.g., prazosin, bunazosine), β-antagonists(e.g., propranolol), and α/β-antagonists (e.g., labetalol, carvedilol);endothelin receptor antagonists; nitric oxide donors/releasingmolecules, including organic nitrates/nitrites (e.g., nitroglycerin,isosorbide dinitrate, amyl nitrite), inorganic nitroso compounds (e.g.,sodium nitroprusside), sydnonimines (e.g., molsidomine, linsidomine),nonoates (e.g., diazenium diolates, NO adducts of alkanediamines),S-nitroso compounds, including low molecular weight compounds (e.g.,S-nitroso derivatives of captopril, glutathione and N-acetylpenicillamine) and high molecular weight compounds (e.g., S-nitrosoderivatives of proteins, peptides, oligosaccharides, polysaccharides,synthetic polymers/oligomers and natural polymers/oligomers),C-nitroso-, O-nitroso- and N-nitroso-compounds, and L-arginine; ACEinhibitors (e.g., cilazapril, fosinopril, enalapril); ATII-receptorantagonists (e.g., saralasin, losartin); platelet adhesion inhibitors(e.g., albumin, polyethylene oxide); platelet aggregation inhibitors,including aspirin and thienopyridine (ticlopidine, clopidogrel) and GPIIb/IIIa inhibitors (e.g., abciximab, epitifibatide, tirofiban,intergrilin); coagulation pathway modulators, including heparinoids(e.g., heparin, low molecular weight heparin, dextran sulfate,β-cyclodextrin tetradecasulfate), thrombin inhibitors (e.g., hirudin,hirulog, PPACK (D-phe-L-propyl-L-arg-chloromethylketone), argatroban),FXa inhibitors (e.g., antistatin, TAP (tick anticoagulant peptide)),vitamin K inhibitors (e.g., warfarin), and activated protein C;cyclooxygenase pathway inhibitors (e.g., aspirin, ibuprofen,flurbiprofen, indomethacin, sulfinpyrazone); natural and syntheticcorticosteroids (e.g., dexamethasone, prednisolone, methprednisolone,hydrocortisone); lipoxygenase pathway inhibitors (e.g.,nordihydroguairetic acid, caffeic acid; leukotriene receptorantagonists; antagonists of E- and P-selectins; inhibitors of VCAM-1 andICAM-1 interactions; prostaglandins and analogs thereof, includingprostaglandins such as PGE1 and PGI2; prostacyclin analogs (e.g.,ciprostene, epoprostenol, carbacyclin, iloprost, beraprost); macrophageactivation preventers (e.g., bisphosphonates); HMG-CoA reductaseinhibitors (e.g., lovastatin, pravastatin, fluvastatin, simvastatin,cerivastatin); fish oils and omega-3-fatty acids; free-radicalscavengers/antioxidants (e.g., probucol, vitamins C and E, ebselen,retinoic acid (e.g., trans-retinoic acid), SOD mimics); agents affectingvarious growth factors including FGF pathway agents (e.g., bFGFantibodies, chimeric fusion proteins), PDGF receptor antagonists (e.g.,trapidil), IGF pathway agents (e.g., somatostatin analogs such asangiopeptin and ocreotide), TGF-β pathway agents such as polyanionicagents (heparin, fucoidin), decorin, and TGF-β antibodies, EGF pathwayagents (e.g., EGF antibodies, receptor antagonists, chimeric fusionproteins), TNF-α pathway agents (e.g., thalidomide and analogs thereof),thromboxane A2 (TXA2) pathway modulators (e.g., sulotroban, vapiprost,dazoxiben, ridogrel), protein tyrosine kinase inhibitors (e.g.,tyrphostin, genistein, and quinoxaline derivatives); MMP pathwayinhibitors (e.g., marimastat, ilomastat, metastat), and cell motilityinhibitors (e.g., cytochalasin B); antiproliferative/antineoplasticagents including antimetabolites such as purine analogs (e.g.,6-mercaptopurine), pyrimidine analogs (e.g., cytarabine and5-fluorouracil) and methotrexate, nitrogen mustards, alkyl sulfonates,ethylenimines, antibiotics (e.g., daunorubicin, doxorubicin, daunomycin,bleomycin, mitomycin, penicillins, cephalosporins, ciprofalxin,vancomycins, aminoglycosides, quinolones, polymyxins, erythromycins,tertacyclines, chloramphenicols, clindamycins, linomycins, sulfonamides,and their homologs, analogs, fragments, derivatives, and pharmaceuticalsalts), nitrosoureas (e.g., carmustine, lomustine) and cisplatin, agentsaffecting microtubule dynamics (e.g., vinblastine, vincristine,colchicine, paclitaxel, epothilone), caspase activators, proteasomeinhibitors, angiogenesis inhibitors (e.g., endostatin, angiostatin andsqualamine), and rapamycin, cerivastatin, flavopiridol and suramin;matrix deposition/organization pathway inhibitors (e.g., halofuginone orother quinazolinone derivatives, tranilast); endothelializationfacilitators (e.g., VEGF and RGD peptide); and blood rheology modulators(e.g., pentoxifylline).

Other examples of therapeutic agents include anti-tumor agents, such asdocetaxel, alkylating agents (e.g., mechlorethamine, chlorambucil,cyclophosphamide, melphalan, ifosfamide), plant alkaloids (e.g.,etoposide), inorganic ions (e.g., cisplatin), biological responsemodifiers (e.g., interferon), and hormones (e.g., tamoxifen, flutamide),as well as their homologs, analogs, fragments, derivatives, andpharmaceutical salts.

Additional examples of therapeutic agents include organic-solubletherapeutic agents, such as mithramycin, cyclosporine, and plicamycin.Further examples of therapeutic agents include pharmaceutically activecompounds, anti-sense genes, viral, liposomes and cationic polymers(e.g., selected based on the application), biologically active solutes(e.g., heparin), prostaglandins, prostcyclins, L-arginine, nitric oxide(NO) donors (e.g., lisidomine, molsidomine, NO-protein adducts,NO-polysaccharide adducts, polymeric or oligomeric NO adducts orchemical complexes), enoxaparin, Warafin sodium, dicumarol, interferons,chymase inhibitors (e.g., Tranilast), ACE inhibitors (e.g., Enalapril),serotonin antagonists, 5-HT uptake inhibitors, and beta blockers, andother antitumor and/or chemotherapy drugs, such as BiCNU, busulfan,carboplatinum, cisplatinum, cytoxan, DTIC, fludarabine, mitoxantrone,velban, VP-16, herceptin, leustatin, navelbine, rituxan, and taxotere.

Therapeutic agents are described, for example, in DiMatteo et al., U.S.patent application Publication No. U.S. 2004/0076582 A1, published onApr. 22, 2004, and entitled “Agent Delivery Particle”, in Pinchuk etal., U.S. Pat. No. 6,545,097, and in Schwarz et al., U.S. Pat. No.6,368,658, all of which are incorporated herein by reference.

While certain embodiments have been described, other embodiments arepossible.

For example, FIG. 10 shows an embolic coil delivery system 800 thatincludes a pushable embolic coil 810 disposed inside a catheter 812.Pushable embolic coils are described, for example, in Elliott et al.,U.S. patent application Publication No. U.S. 2006/0116711 A1, publishedon Jun. 1, 2006, and entitled “Embolic Coils”, and in Buiser et al.,U.S. patent application Ser. No. 11/430,602, filed on May 9, 2006, andentitled “Embolic Coils”, both of which are incorporated herein byreference. A pusher wire 814 includes a blunt end 816 that contacts aproximal end 818 of embolic coil 810 rather than an end fitting forengaging a detachable coil. Fiber bundles 820 extending proximally fromtheir attachment points 826 are disposed on a proximal half 822 of coil810 but not on a distal half 824 of coil 810. Because pushable coilstend to be shorter than detachable coils, some pushable coils can beloaded into catheters by inserting the pushable coil into the proximalend of a catheter and pushing the coil into place.

In another example, embolic coil delivery systems can include a varyingfiber bundle distribution without orienting the fiber bundles such thatthe fiber bundles extend proximally from their attachment point to theassociated coil wire.

Accordingly, other embodiments are within the scope of the followingclaims.

1-20. (canceled)
 21. A system comprising: a catheter having a deliveryend; and an embolic coil at least partially disposed within thecatheter, the embolic coil including a coil wire having an end fittingconfigured to releasably couple to an end fitting of a delivery wire,and multiple fiber bundles contacting the catheter, each fiber bundlehaving a first bundle end attached to the coil wire and a second bundleend opposite the first bundle end; wherein more fiber bundles areattached to a first half of the coil adjacent the end fitting than areattached to a second half of the coil.
 22. The system of claim 21,wherein spacing between adjacent fiber bundles increases with increasingdistance from the end fitting of the coil wire.
 23. The system of claim21, wherein the fiber bundles are disposed in at least one group and thespacing between adjacent fiber bundles is constant within each group ofthe at least one group.
 24. The system of claim 21, wherein each fiberbundle is attached to the coil wire at an attachment point and a firstattachment point is circumferentially spaced apart from a secondattachment point.
 25. The system of claim 24, wherein the attachmentpoint of each fiber bundle is circumferentially spaced apart from theattachment points of adjacent fiber bundles.
 26. The system of claim 21,wherein the fiber bundle comprises polyethylene terephthalate or nylon.27. The system of claim 21, wherein the coil wire has a diameter from0.0075 inch to 0.015 inch.
 28. The system of claim 21, wherein amajority of the fiber bundles are angled such that a distance from thefirst bundle end of a specific fiber bundle to the delivery end of thecatheter is less than a distance from the second bundle end of thespecific fiber bundle to the delivery end of the catheter.
 29. Thesystem of claim 21, wherein the coil wire comprises a metal.
 30. Thesystem of claim 21, further comprising a lubricant disposed on the fiberbundles.
 31. The system of claim 21, wherein an inner surface of thecatheter comprises a material selected from the group consisting ofpolypropylene, polytetrafluoroethylene (PTFE), fluoroethylene polymer(FEP), low-density polyethylene (LDPE), high-density polyethylene(HDPE), nylon, Teflon®, and acrylic.
 32. A system comprising: a deliverywire with an end fitting; a coil wire having a first end, an oppositesecond end, and a midpoint located halfway between the first end and thesecond end; an end fitting at the first end of the coil wire, the endfitting configured to releasably couple the embolic coil to the endfitting of the delivery wire; and multiple fiber bundles attached to thecoil wire; wherein more fiber bundles are attached to the coil wirebetween the first end and the midpoint than are attached to the coilwire between the second end and the midpoint, and wherein the coil is anembolic coil.
 33. The system of claim 32, wherein spacing betweenadjacent fiber bundles increases with increasing distance from the firstend of the coil.
 34. The system of claim 32, wherein the fiber bundlesare disposed in at least one group and the spacing between adjacentfiber bundles is constant within each group of the at least one group.35. The system of claim 32, wherein a proximal end of the coil wire isconfigured to provide an opposable surface configured for engagement ofa pusher element.
 36. A system comprising: a catheter having a deliveryend; a delivery wire with an end fitting; and an embolic coil disposedwithin the catheter, the embolic coil having a first half and a secondhalf, the second half disposed between the first half and the deliveryend of the catheter, the embolic coil including a coil wire and multiplefiber bundles contacting the catheter, the coil wire having an endfitting configured to releasably couple to the end fitting of thedelivery wire and each fiber bundle extending from a first bundle endattached to the coil wire to a second bundle end opposite the firstbundle end; and wherein more fiber bundles are attached to the firsthalf of the embolic coil than are attached to a second half of the coil.37. The system of claim 36, wherein spacing between adjacent fiberbundles increases with increasing distance from the end fitting of thecoil wire.
 38. The system of claim 36, wherein the fiber bundles aredisposed in groups and the spacing between adjacent fiber bundles isconstant within each group.
 39. The system of claim 36, wherein eachfiber bundle is attached to the coil wire at an attachment point and afirst attachment point is circumferentially spaced apart from a secondattachment point.
 40. The system of claim 39, wherein the attachmentpoint of each fiber bundle is circumferentially spaced apart from theattachment points of adjacent fiber bundles.